Weak functional coupling of the melanocortin-1 receptor expressed in human adipocytes.
The melanocortin (MC) receptor type-1 (MC1-R) is the only one of the five MC receptor subtypes expressed in human adipose tissue explants, human mesenchymal stem cells (MSCs), and MSC-derived adipocytes. Following our recent expression studies (Obesity 2007, 15, 40-49), we now investigated the functional role of MC1-R in these tissues and cells to deduce the coupling state of MC1-R to intracellular output signals in human fat cells and tissue. Expression of MC1-R by undifferentiated and differentiated MSCs was quantified by real-time TaqMan PCR. Intracellular output signals (cAMP, lipolysis, secretion of IL-6, IL-10, and TNF-alpha), as well as effects on the metabolic rate and proliferation of human MSCs were analyzed by standard assays, exposing undifferentiated and differentiated MSCs and, in part, human adipose tissue explants to the potent MC1-R agonist, [Nle(4), D-Phe(7)]-alpha-MSH (NDP-MSH). This agonist induced a weak cAMP signal in MSC-derived adipocytes. However, it did not affect lipolysis in these cells or in adipose tissue explants, nor did it modulate cytokine release and mRNA expression of IL-6, IL-8, and TNF-alpha upon LPS stimulation. In undifferentiated MSCs, NDP-MSH did not alter the metabolic rate, but it showed a significant antiproliferative effect. Therefore, it appears that MC1-R-effector coupling in (differentiated) human adipocytes is too weak to induce a regulatory effect on lipolysis or inflammation; by contrast, MC1-R stimulation in undifferentiated MSCs induces an inhibitory signal on cell proliferation.
Hoch
Matthias
M
Department of Biomedicine, University Hospital, Basel, Switzerland.
Hirzel
Estelle
E
Lindinger
Peter
P
Eberle
Alex N
AN
Linscheid
Philippe
P
Martin
Ivan
I
Peters
Thomas
T
Peterli
Ralph
R
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000345:Affinity Labels / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000187:drug effects / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D044102:Receptor, Melanocortin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
D000345:Affinity Labels; D016588:Anticarcinogenic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D044102:Receptor, Melanocortin, Type 1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-